SLC-mediated transmembrane transport

According to the Human Genome Organization (HUGO) Gene Nomenclature Committee, all human transporters can be grouped into the solute-carrier (SLC) superfamily (http://www.genenames.org/genefamilies/SLC). Currently, there are 55 SLC families in the superfamily, with a total of at least 362 putatively functional protein-coding genes (Hediger et al. 2004, He et al. 2009; http://www.bioparadigms.org/slc/intro.htm). At least 20-25% amino-acid sequence identity is shared by members belonging to the same SLC family. No homology is shared between different SLC families. While the HUGO nomenclature system by definition only includes human genes, the nomenclature system has been informally extended to include rodent species through the use of lower cases letters (e.g., Slc1a1 denotes the rodent ortholog of the human SLC1A1 gene). And it's worthwhile to mention that pumps, channels and aquaporins are not included in SLC superfamily.

To date, nine SLC gene families (SLC4, SLC5, SLC8, SLC9, SLC12, SLC20, SLC24, SLC26 and SLC34) comprise the group that exclusively transports inorganic cations and anions across membranes. A further eight SLC gene families (SLC1, SLC6, SLC7, SLC16, SLC25, SLC36, SLC38 and SLC43) are involved in the transport of amino acids and oligopeptides. Two gene families are responsible for glucose transport in humans. SLC2 (encoding GLUTs) and SLC5 (encoding SGLTs) families mediate glucose absorption in the small intestine, glucose reabsorption in the kidney, glucose uptake by the brain across the blood-brain barrier and glucose release by all cells in the body.

SLC transporters are able to transport bile salts, organic acids, metal ions and amine compounds. Myo-Inositol is a precursor to phosphatidylinositols (PtdIns) and to the inositol phosphates (IP), which serve as second messengers and also act as key regulators of many cell functions. Mono-, di- and tri-carboxylate transporters mediate the transport of these acids across cellular membranes. Essential metals are transported by metal-transporting proteins, which also control their efflux to avoid toxic build-up. The SLC6 gene family encodes proteins that mediate neurotransmitter uptake in the central nervous system (CSN) and peripheral nervous system (PNS), thus terminating a synaptic signal. Urea transport is particularly important in the process of urinary concentration and for rapid urea equilibrium in non-renal tissues. Choline uptake is the rate-limiting step in the synthesis of the neurotransmitter acetylcholine. SLC genes SLC5A7 and the SLC44 family encode choline transporters. The SLC22 gene family of solute carriers function as organic cation transporters (OCTs), cation/zwitterion transporters (OCTNs) and organic anion transporters (OATs). They play important roles in drug absorption and excretion. Substrates include xenobiotics, drugs, and endogenous amine compounds.

The human SLC5A6 encodes the Na+-dependent multivitamin transporter SMVT. SMVT co-transports biotin (vitamin B7), D-Pantothoate (vitamin B5) and lipoic acid into cells with Na+ ions electrogenically. Four SLC gene families encode transporters that play key roles in nucleoside and nucleobase uptake for salvage pathways of nucleotide synthesis, and in the cellular uptake of nucleoside analogues used in the treatment of cancers and viral diseases. The human gene SLC33A1 encodes acetyl-CoA transporter AT1. Acetyl-CoA is transported to the lumen of the Golgi apparatus, where it serves as the substrate of acetyltransferases that O-acetylates sialyl residues of gangliosides and glycoproteins. Nucleotide sugars are used as sugar donors by glycosyltransferases to create the sugar chains for glycoconjugates such as glycoproteins, polysaccharides and glycolipids. The human solute carrier family SLC35 encode nucleotide sugar transporters (NSTs), localised on Golgi and ER membranes, which can mediate the antiport of nucleotide sugars in exchange for the corresponding nucleoside monophosphates (eg. UMP for UDP-sugars). Long chain fatty acids (LCFAs) can be used for energy sources and steroid hormone synthesis and regulate many cellular processes such as inflammation, blood pressure, the clotting process, blood lipid levels and the immune response. The SLC27A family encode fatty acid transporter proteins (FATPs). The SLC gene family members SLCO1 SLCO2 and SLCO3 encode organic anion transporting polypeptides (OATPs). OATPs are membrane transport proteins that mediate the sodium-independent transport of a wide range of amphipathic organic compounds including bile salts, steroid conjugates, thyroid hormones, anionic oligopeptides and numerous drugs.